Wolf-Hirschhorn Syndrome

What is Wolf-Hirschhorn syndrome?

Wolf-Hirschhorn syndrome is a genetic condition that occurs when someone is missing genetic material at the tip of one of their chromosome 4s. Another name for this condition is 4p- syndrome. This condition affects several different parts of your child’s body including their heart and brain, which could lead to seizures. Children diagnosed with this condition have distinct facial characteristics, like wide-set eyes and a small head. Wolf-Hirschhorn syndrome also causes problems with intellectual development and growth.

Who does Wolf-Hirschhorn syndrome affect?

Wolf-Hirschhorn syndrome can affect anyone since it’s a genetic condition. Most cases aren’t inherited, meaning your parent’s don’t pass the condition onto you. Instead, the condition is the result of a random (de novo) chromosome deletion during either egg or sperm development or early in embryonic development. People who experience a de novo chromosome change don’t have a history of the condition in their family.

Studies show that children assigned female at birth are more likely to have Wolf-Hirschhorn syndrome over children assigned male at birth.

How common is Wolf-Hirschhorn syndrome?

Wolf-Hirschhorn syndrome affects an estimated 1 out of every 50,000 births. This estimate could be low because some children with very mild symptoms never receive an official diagnosis or their symptoms are misdiagnosed as another genetic condition.

What are the symptoms of Wolf-Hirschhorn syndrome?

Symptoms of Wolf-Hirschhorn syndrome affect different parts of your child’s body. Each child has symptoms that range in severity.

Facial characteristics

Children diagnosed with Wolf-Hirschhorn syndrome have symptoms that affect their facial features, including:

• Cleft palate or cleft lip.
• Facial features that are different sizes on each side of the face (asymmetrical).
• Flat nasal bridge.
• High forehead.
• Low-set or malformed ears.
• Missing teeth.
• Small chin (micrognathia).
• Small head.
• Wide-set, bulging eyes.

Growth and development symptoms

Before your child is born, they will grow slowly in the womb. When they’re born, this can cause infants to have:

• A weak muscle tone (hypotonia) or underdeveloped muscles.
• Delayed developmental milestones like sitting, standing and walking.
• Problems feeding.
• Trouble gaining weight.

These growth and developmental delays can cause your child to have short stature.

Symptoms that affect the brain

Children born with Wolf-Hirschhorn syndrome can have problems with cognitive development (intellectual disability) that range from mild to severe. Studies show that children may have excellent social skills but might struggle with language and communicating.

Your child could have seizures throughout childhood that can be resistant to treatment. As your child gets older, their seizures can lessen or go away.

Body systems symptoms

Symptoms of Wolf-Hirschhorn syndrome target other parts of your child’s body, which could cause:

• Curve of the spine (scoliosis or kyphosis).
• Dry skin.
• Heart growth complications (atrial septal defect).
• Immune system deficiency that causes increased infections.
• Kidney function problems.
• Problems in the urinary tract and reproductive organs (genitourinary tract).
• Vision problems.

What causes Wolf-Hirschhorn syndrome?

Missing genes (deletion) on the short arm of chromosome 4 (4p-) causes Wolf-Hirschhorn syndrome. Chromosome deletion occurs either during the formation of the egg or sperm, or embryonic development when the egg and sperm meet. During this time, reproductive cells don’t copy the chromosomes exactly, which causes part of the chromosome not to appear where it should.

In rare cases, a ring chromosome causes Wolf-Hirschhorn syndrome. This occurs when a chromosome breaks in two places, then fuses together in a circular shape like a ring. When the chromosomes fuse together, part of the chromosome breaks off and removes itself from your child’s genetic code.

When your child loses part of their chromosome, their genes don’t have the instructions they need to build their body. This causes symptoms of Wolf-Hirschhorn syndrome. The amount of the chromosome that’s missing is different for each person. If your child is missing a large part of chromosome 4, they’ll have more severe symptoms.

Can you inherit Wolf-Hirschhorn syndrome?

A small percentage of cases can pass from one parent to their child during conception. In these cases, the biological parents have a balanced translocation; this means that two or more chromosomes broke, and the pieces switched places and reattached. People with balanced translocations are healthy but they are more likely to have a child who inherits an unbalanced form of the translocation, meaning that there are extra/missing pieces of chromosomes. If the translocation causes 4p16.3 to be absent/deleted, the child will have Wolf-Hirschhorn syndrome. Balanced translocations can run through families.

How is Wolf-Hirschhorn syndrome diagnosed?

Your provider will suspect Wolf-Hirschhorn syndrome during early childhood if your child has the following symptoms:

• Facial characteristics.
• Growth problems.
• Developmental delays.
• Seizures.

What tests diagnose Wolf-Hirschhorn syndrome?

Your provider will confirm the diagnosis with a genetic test called a chromosome microarray, which is a genetic test that identifies changes to your child’s chromosomes via a small sample of their blood, saliva or cheek cells. Once your provider has a sample from your child, they will examine your child’s DNA.

If the test shows a specific piece of chromosome 4 is missing (4p16.3), your child will receive a Wolf-Hirschhorn syndrome diagnosis.

How is Wolf-Hirschhorn syndrome treated?

Treatment for Wolf-Hirschhorn syndrome addresses specific symptoms. Treatment could include:

• Surgery to repair growth abnormalities, especially the heart.
• Physical or occupational therapy to build muscle tone.
• Educational programs (special education) to help with cognitive development.
• Medicine to treat seizures.

Your family might benefit from genetic counseling. Genetic counselors can help you learn more about your child’s diagnosis and how to support them.

Who treats Wolf-Hirschhorn syndrome?

Your child will need to see different providers throughout their childhood to make sure they’re healthy and that symptoms aren’t affecting their ability to thrive. After your child receives a diagnosis, they will most likely need evaluations and regular checkups from the following providers:

• A neurologist to examine their brain.
• A cardiologist to examine their heart.
• A dentist to maintain the health of their teeth.
• An optometrist to examine their eyes.

Your primary care provider might recommend regular blood tests to monitor your child’s kidney function during annual visits.

How can I prevent Wolf-Hirschhorn syndrome?

Since Wolf-Hirschhorn syndrome is most often the result of a random (de novo) genetic mutation, you can’t prevent the condition. Although rare, some children inherit the condition from their parents. To better understand your risk of passing a genetic condition onto your child, talk to your provider about genetic testing and genetic counseling.

What can I expect if my child has Wolf-Hirschhorn syndrome?

There’s no cure for Wolf-Hirschhorn syndrome, but treatment to address your child’s symptoms can lead to a positive outcome.

The prognosis for people diagnosed with Wolf-Hirschhorn syndrome depends on the severity of their symptoms. Symptoms that affect a person’s heart and brain can shorten their life expectancy, but many children diagnosed with the condition survive into adulthood with care and treatment.

When should I see my child’s healthcare provider?

Visit your child’s healthcare provider if they:

• Have a wound that won’t heal (looks crusty, leaks a clear to yellow pus).
• Get frequent colds (fever, cough, sore throat) that don’t seem to go away.
• Miss developmental milestones.
• Aren’t eating regularly.
• Have an irregular heartbeat, shortness of breath or fatigue (signs of atrial septal defect).

When should I take my child to the ER?

Your child, diagnosed with Wolf-Hirschhorn syndrome, is at risk of having seizures. A seizure causes your child to:

• Temporarily lose consciousness between 30 seconds and two minutes.
• Have convulsions where they move their arms and legs uncontrollably.

If this occurs, call 911 immediately or take your child to the emergency room.

What questions should I ask my doctor?

• Are there side effects to the medicine you prescribed?
• How severe is my child’s diagnosis?
• What should I do if my child misses developmental milestones?
• Does my child need to visit a specialist?

A note from Cleveland Clinic

It may be difficult to hear that your child has a genetic condition like Wolf-Hirschhorn syndrome. While there may be a few bumps in the road caused by symptoms of the condition, your provider will offer a treatment plan and will work closely with specialists to help your child have a happy and healthy life. To gain a better awareness of your child’s condition and how you can support them during their diagnosis, talk to your provider about genetic counseling.